本文選題：血管內(nèi)皮生長(zhǎng)因子 + 內(nèi)皮抑素　； 參考：《瀘州醫(yī)學(xué)院》2012年碩士論文

【摘要】：目的：研究川崎病(KD)患兒在急性期及恢復(fù)期血中血管內(nèi)皮生長(zhǎng)因子（VEGF）、內(nèi)皮抑素（ES）、熱休克蛋白60（HSP60）及熱休克蛋白70（HSP70）的表達(dá)水平，探討KD急性期與恢復(fù)期血清中VEGF與ES的相關(guān)性分析研究，并研究其表達(dá)對(duì)KD冠脈損害的影響，進(jìn)而為研究及預(yù)防冠脈損害提供相應(yīng)的理論依據(jù)。 方法：1.標(biāo)本采集：（1）研究組：KD患兒25例，其中冠脈損害組（CAL）10例，冠脈正常組（NCAL）15例，分別采集急性期（靜脈使用IVIG前，病程1-2周）、恢復(fù)期（靜脈使用IVIG后，病程3-4周）外周血制備血清。（2）對(duì)照組：分別采集20例年齡相仿的正常健康患兒（空白對(duì)照組，C組）及20例年齡相仿的發(fā)熱患兒（發(fā)熱對(duì)照組，F(xiàn)組）外周血制備血清。 2.指標(biāo)檢測(cè)：分別用雙抗體夾心法（ELISA）測(cè)定各組血管內(nèi)皮生長(zhǎng)因子（VEGF）、內(nèi)皮抑素（ES）、熱休克蛋白60（HSP60）及熱休克蛋白70（HSP70）的表達(dá)水平。 3.統(tǒng)計(jì)學(xué)處理：運(yùn)用SPSS17.0行統(tǒng)計(jì)學(xué)分析，數(shù)據(jù)都采取以均數(shù)加減標(biāo)準(zhǔn)差（X+S）表示。組間比較用單因素方差分析(one-way analysisof variance，ANOVA)，兩兩比較采用LSD檢驗(yàn)；VEGF/ES比值用秩和檢驗(yàn)。VEGF與ES的相關(guān)性分析采用Bivariate法，，檢驗(yàn)水準(zhǔn)為0.05（雙側(cè)），P0.05為差異有統(tǒng)計(jì)學(xué)意義。 結(jié)果：1.VEGF、ES、VEGF/ES （1）KD急性期血清VEGF（1123.82±80.31）水平與KD恢復(fù)期（586.65±78.38）、發(fā)熱對(duì)照組（306.43±67.92）和空白對(duì)照組（244.65±69.10）相比明顯升高（P均0.01）；KD恢復(fù)期血清VEGF（586.65±78.38）水平與發(fā)熱對(duì)照組（306.43±67.92）和空白對(duì)照組（244.65±69.10）相比明顯升高（P均0.01）。（2）KD急性期血清ES水平（173.23±5.41）與發(fā)熱對(duì)照組（188.17±5.25）相比明顯降低（P0.05）；和空白對(duì)照組（195.30±5.84）相比明顯降低（P0.01）；與KD恢復(fù)期（180.44±6.03）相比較，無(wú)明顯統(tǒng)計(jì)學(xué)意義（P0.05）。（3）KD恢復(fù)期血清ES水平（180.44±6.03）與發(fā)熱對(duì)照組（188.17±5.25）和空白對(duì)照組（195.30±5.84）相比明顯降低（P均0.05）。（4）KD急性期血清VEGF/ES（6.89±1.02×10~(-3)）與KD恢復(fù)期（3.95±0.76×10~(-3)）、發(fā)熱對(duì)照組（1.64±0.20×10~(-3)）和空白對(duì)照組（1.26±0.18×10~(-3)）相比明顯升高（P均0.01）；KD恢復(fù)期VEGF/ES（3.95±0.76×10~(-3)）與發(fā)熱對(duì)照組（1.64±0.20×10~(-3)）和空白對(duì)照組（1.26±0.18×10~(-3)）相比明顯升高（P均0.01）。（5）發(fā)熱對(duì)照組血清VEGF（306.43±67.92）、ES（188.17±5.25）、VEGF/ES（1.64±0.20×10~(-3)）與空白對(duì)照組相比VEGF（244.65±69.10）、ES（195.30±5.84）、VEGF/ES（1.26±0.18×10~(-3)），無(wú)明顯統(tǒng)計(jì)學(xué)意義（P均0.05）。（6）川崎病CAL組血清VEGF （1260.23±82.65）、 VEGF/ES（6.91±0.88×10~(-3)）和NCAL組血清VEGF（976.54±76.30）、VEGF/ES（4.12±0.65×10~(-3)）相比較明顯增高（P均0.01）；川崎病CAL組血清ES水平（168.42±8.40）和NCAL組（188.54±7.85）相比較明顯降低，差異有統(tǒng)計(jì)學(xué)意義（P0.01）。 2.VEGF與ES的相關(guān)性分析 KD急性期血清VEGF與ES呈顯著性負(fù)相關(guān)（r=-0.642，P0.01）；KD恢復(fù)期血清VEGF與ES呈顯著性負(fù)相關(guān)（r=-0.806，P0.01）。 3. HSP60、HSP70 （1）KD急性期血清HSP60水平（4557.30±432.71）與KD恢復(fù)期（3987.43±378.95）、發(fā)熱對(duì)照組（3894.50±564.33）、空白對(duì)照組（3871.23±489.40）相比較明顯增高（P均0.01）。（2）KD急性期血清HSP70水平（4633.28±679.33）較KD恢復(fù)期（4027.14±595.25）、發(fā)熱對(duì)照組（3410.15±674.10）、空白對(duì)照組（3396.50±639.23）明顯增高（P均0.01）。（3）KD恢復(fù)期血清HSP60（3987.43±378.95）與發(fā)熱對(duì)照組（3894.50±564.33）、空白對(duì)照組（3871.23±489.40）相比較，差異無(wú)明顯統(tǒng)計(jì)學(xué)意義（P均0.05）。（4）KD恢復(fù)期血清HSP70（4027.14±595.25）與發(fā)熱對(duì)照組（3410.15±674.10）、空白對(duì)照組（3396.50±639.23）相比較明顯增高，差異有統(tǒng)計(jì)學(xué)意義（P均0.01）。（5）發(fā)熱對(duì)照組HSP60（3894.50±564.33）、HSP70（3410.15±674.10）和空白對(duì)照組HSP60（3871.23±489.40）、HSP70（3396.50±639.23）相比較，無(wú)明顯統(tǒng)計(jì)學(xué)意義（P均0.05）（。6）KD患兒CAL組血清HSP60（4779.34±564.31）較NCAL組（3874.27±478.37）明顯增高，差異有統(tǒng)計(jì)學(xué)意義（P0.01）；KD患兒CAL組血清HSP70（3569.37±603.34）較NCAL組（4899.40±637.21）明顯降低，差異有統(tǒng)計(jì)學(xué)意義（P0.05）。 結(jié)論：1.在KD急性期中血清VEGF、VEGF/ES明顯升高，而恢復(fù)期二者雖有所下降，但仍處于一個(gè)相對(duì)高的水平；而急性期血清ES水平明顯降低，在恢復(fù)期血清ES水平仍處于一個(gè)低水平。川崎病CAL組血清VEGF、VEGF/ES較NCAL組相比均明顯增高；川崎病CAL組血清ES水平較NCAL組相比明顯降低。提示VEGF、ES不僅參與了KD早期血管炎癥過(guò)程，而且高水平的VEGF、VEGF/ES可能參與了KD中持久的冠脈損傷。 VEGF、VEGF/ES可作為川崎病冠脈損害的危險(xiǎn)因素之一，在KD血管壁的損傷與冠脈瘤的形成中起重要作用，而ES在病程中起到抑制血管炎性反應(yīng)的作用。 2.血清VEGF與ES在KD急性期、恢復(fù)期均呈顯著性負(fù)相關(guān)（r=-0.642，P0.01；r=-0.806，P0.01）。提示ES在KD病程能夠在一定程度上抑制VEGF的作用，起到抑制冠脈損害的功能；VEGF與ES之間的平衡參與了KD血管壁的重構(gòu)。 3. KD急性期患兒血清HSP60、HSP70水平明顯增高，而恢復(fù)期血清HSP60顯著下降，HSP70仍維持在一個(gè)高水平。KD患兒CAL組血清HSP60水平顯著較NCAL組高，而CAL組血清HSP70水平顯著較NCAL組低，提示在冠脈損害發(fā)生情況中，HSP60是作為一個(gè)危險(xiǎn)因素存在，可能與“抗原模擬宿主學(xué)說(shuō)”有關(guān);熱休克蛋白70在冠脈損害過(guò)程中，可能起保護(hù)作用，抑制血管炎性反應(yīng)的發(fā)生。急性期高水平的HSP60、HSP70提示二者在KD急性期中均積極的參與了血管炎性反應(yīng)，HSP60促進(jìn)血管炎性反應(yīng)，而HSP70起了抑制作用；恢復(fù)期HSP70仍維持在一個(gè)高水平，提示HSP70對(duì)血管炎性反應(yīng)的抑制可以持續(xù)到病程的恢復(fù)期。
[Abstract]:Objective : To investigate the expression level of vascular endothelial growth factor ( VEGF ) , endothelin ( ES ) , heat shock protein 60 ( HSP60 ) and heat shock protein 70 ( HSP70 ) in children with KD .

Methods : 1 . Specimens were collected : ( 1 ) study group : 25 patients with KD , 10 patients with coronary lesion group ( CAL ) and 15 normal controls ( NCAL ) .

2 . Target detection : The expression levels of VEGF , ES , HSP60 and HSP70 were determined by ELISA .

3 . Statistical treatment : SPSS 17.0 was used to analyze the statistical analysis . The data was expressed by mean addition and subtraction standard deviation ( X + S ) . One - way ANOVA of variance ( ANOVA ) was used to compare the two comparisons .
The correlation analysis of VEGF and ES showed that the level of VEGF and ES was 0.05 ( bilateral ) and P 0.05 was statistically significant .

Results : 1 . VEGF , ES , VEGF / ES

( 1 ) The serum VEGF ( 1123 . 82 鹵 80.31 ) levels in KD acute phase were significantly higher than those in KD recovery period ( 586.65 鹵 78.38 ) , fever group ( 306.43 鹵 67.92 ) and blank control group ( 244.65 鹵 69.10 ) ( P < 0.01 ) .
The serum levels of VEGF ( 586.65 鹵 78.38 ) in KD recovery period were significantly higher than that in the control group ( 306.43 鹵 67.92 ) and the control group ( 244.65 鹵 69.10 ) ( P < 0.01 ) .
Compared with the blank control group ( 195.30 鹵 5.84 ) , there was a significant decrease ( P0.01 ) .
( 4 ) The serum VEGF / ES ( 6.89 鹵 1.02 脳 10 ~ ( -3 )) and KD recovery period ( 3.95 鹵 0.76 脳 10 ~ ( -3 )) and the control group ( 1.26 鹵 0.18 脳 10 ~ ( -3 )) were significantly higher than those in the control group ( 1.64 鹵 0.20 脳 10 ~ ( -3 )) and the control group ( 1.26 鹵 0.18 脳 10 ~ ( -3 )) ( P < 0.01 ) .
VEGF / ES ( 3.95 鹵 0.76 脳 10 ~ ( -3 )) in KD recovery period was significantly higher than that in control group ( 1.64 鹵 0.20 脳 10 ~ ( -3 )) and blank control group ( 1.26 鹵 0.18 脳 10 ~ ( -3 )) . The serum VEGF ( 126.23 鹵 82.65 ) , VEGF / ES ( 6.91 鹵 0.88 脳 10 ~ ( -3 )) , VEGF / ES ( 6.91 鹵 0.88 脳 10 ~ ( -3 )) and VEGF / ES ( 4.12 鹵 0.65 脳 10 ~ ( -3 )) were significantly higher than those in control group ( P < 0.01 ) .
The serum ES level ( 168.42 鹵 8.40 ) and the NCAL group ( 188.54 鹵 7.85 ) decreased significantly in the CAL group of Kawasaki disease ( P0.01 ) .

2 . Correlation between VEGF and ES

There was a negative correlation between serum VEGF and ES in KD acute phase ( r = - 0.642 , P0.01 ) .
There was a significant negative correlation between serum VEGF and ES in KD recovery period ( r = - 0.806 , P0.01 ) .

3. HSP60,HSP70


( 3 ) The serum HSP60 ( 3987.43 鹵 375.25 ) and the control group ( 3871.23 鹵 489.40 ) and the control group ( 3871.23 鹵 489.40 ) were significantly higher than those in the control group ( 3894.50 鹵 564.33 ) and the control group ( 3871.23 鹵 489.40 ) . The serum HSP60 ( 4779.34 鹵 564.31 ) in the KD recovery period was significantly higher than that in the control group ( 3874.27 鹵 474.31 ) .
Compared with the NCAL group ( 4899.40 鹵 637.21 ) , the serum HSP70 ( 3569.37 鹵 603.34 ) decreased significantly in the CAL group ( P0.05 ) .

Conclusion : 1 . Serum VEGF and VEGF / ES increased significantly in the acute phase of KD , while the recovery period decreased , but remained at a relatively high level .
The serum ES level in the acute phase was significantly lower than that in NCAL group , but the serum ES level was still at a low level during the recovery period .
The levels of serum ES in patients with Kawasaki disease were significantly lower than those in NCAL group , suggesting that VEGF and ES were not only involved in the early stage of vascular inflammation in KD , but VEGF and VEGF / ES might participate in the long - lasting coronary artery injury in KD . Vascular endothelial growth factor ( VEGF ) and VEGF / ES play an important role in the pathogenesis of Kawasaki disease .

2 . There was a significant negative correlation between serum VEGF and ES in KD acute stage and recovery period ( r = - 0.642 , P0.01 ) .
r=-0.806,P0.01). It is suggested that ES can inhibit VEGF to some extent in KD course , and play a role in inhibiting coronary lesion ;
The equilibrium between VEGF and ES is involved in the reconstruction of the KD vessel wall .

The levels of HSP60 and HSP70 in serum HSP60 and HSP70 in children with KD were significantly higher than those in NCAL group , but the level of HSP70 in CAL group was significantly lower than that in NCAL group .
HSP70 was maintained at a high level during the recovery period , suggesting that the inhibition of HSP70 on vascular inflammatory response can persist to the recovery period of the course .
【學(xué)位授予單位】：瀘州醫(yī)學(xué)院
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2012
【分類(lèi)號(hào)】：R725.4

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